The use of recombinant bispecific antibodies (bsabs) for retargeting effector T lymphocytes towards cancer cells is recently emerging as a promising immunotherapeutic tool for the treatment of hematologic malignancies and other cancers. The high efficacy of this class of molecules in redirecting specifically CD8+ and CD4+ T cells to any chosen tumor associated antigen (TAA) on the surface of tumor cells by cross-linking their activating CD3 receptor has been reported in many preclinical and clinical studies. Nonetheless, due to their low molecular mass, bsabs have a short half-life in vivo and consequently have to be continuously administered to patients over prolonged time spans of several weeks to achieve clinical responses (Schlereth et al. 2005, Stork et al. 2008, Bargou et al. 2008, Handgretinger et al. 2011). External medical pump devices as currently used in clinical trials can be a potential source of infection. Thus there is a need to improve the route of application for this highly effective class of drugs for treating disorders such as cancer. An alternative to continuous infusion through external medical pump devices are gene-modified cells, which continuously produce and secrete bsabs for their life-time in the body of the patient.
Kasuya, et al. (Kasuya et al., Int. J. Mol Med, 25, 2010, 209-215) report the production of a bispecific anti-HER2 and anti-CD16 antibody by embryonic fibroblasts that have been transplanted into immunodeficient mice.
In addition Compte and colleagues, (Compte, et al., Stem Cells, 2099, 27, 753-760) disclose a tumor immunotherapy by use of gene-modified human mesenchymal stem cells (hMSC) for producing a bispecific anti-CEA and anti-CD3 antibody.
Furthermore Frank, et al. (Frank, et al., PloSone, 2009, 4, e831) used neural stem cells (NSC) as a novel platform for tumor specific delivery of therapeutic antibodies.
Although several advances in the use of genetically modified cells for producing therapeutic antibodies have been made, there are still limitations that have to be overcome.
The present invention is directed to overcoming these and other deficiencies in the art.